Although the exact nutrient composition of the L. pneumophila replication vacuole is unknown, several lines of evidence indicate that amino acids are critical, and differences in these concentrations can affect the differentiation state of the microbe. Foremost, broth studies indicate that L. pneumophila depends on amino acids for its sole source of carbon and energy (Tesh et al. 1983). Additionally, the uptake of amino acids by its host cell via the human transporter protein SLC1A5 (hATB0,+) is required for L. pneumophila to replicate in macrophages (Wieland et al. 2005). Furthermore, L. pneumophila uses amino acid transporters to determine the nutrient availability of the environment and trigger its differentiation as deemed appropriate (discussed below) (Sauer et al. 2005). Finally, when amino acids are depleted, L. pneumophila utilizes the stringent response to induce a panel of traits that enable escape from its spent host, survival in the environment, and the capacity to invade another suitable host (discussed below) (Hammer and Swanson 1999). The regulatory linkage of nutrient availability to differentiation is essential for L. pneumophila pathogenesis as it determines the phenotypic profile of the microbe.
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